In the past three years, the knowledge on the protein composition of blood has been greatly improved; for example the number of proteins identified in blood has increased 30 fold from 300 to almost 10.000. We discuss the techniques used to separate these proteins, in particular liquid chromatography coupled to mass spectrometry. By applying in-silico digestion and separation on the most recent list of known serum proteins, we study separation schemes and apply this to searching for protein biomarkers signalling disease.